Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts

Abstract

Glycosphingolipids (GSLs) are complex macromolecules on cell membranes that have been shown to play a role in neutrophil differentiation, activation, phagocytosis, and adhesion to both microorganisms and vascular endothelium. Because GSLs are often cryptic antigens on cell membranes, little is known regarding GSL expression in early myelopoiesis. To study the latter, myeloblasts were collected from patients with acute nonlymphocytic leukemia (ANLL) who required therapeutic leukocytopheresis for hyperleukocytosis. The neutral GSLs were isolated and identified by high-performance thin-layer chromatography (HPTLC), HPTLC immunostaining, gas chromatography, nuclear magnetic resonance, and fast atom bombardment-mass spectrometry. Like mature peripheral blood neutrophils, myeloblasts expressed glucosylceramide, lactosylceramide, and the neolacto-family GSLs, lactotriaosylceramide and neolactotetraosylceramide. Unlike neutrophils and chronic myeloid leukemia, most ANLL samples also expressed the globo-series GSLs, globotriaosylceramide and globotetraosylceramide. Globo GSL expression was strongly associated with a myeloblastic (ANLL M0-M2) and monoblastic phenotype (M5). A weak association was also noted with expression of either lymphoid (P < .

Monoclonal antibody B2, a marker of neuroendocrine sympathoadrenal precursors, recognizes the Luke (LKE) antigen

“…Individual GSLs were identified based on their relative mobility (R f ) to standards and immunoreactivity with MoAbs. GSL standards were purchased from Sigma Chemical Co. or isolated previously in our laboratory 11,12 . Staining intensity was determined by scanning densitometry of digitally scanned images (Quantiscan, Biosoft, Ferguson, MO).…”

“…Plates were dried and then blocked with Tris buffer (50 mmol/L Tris‐HCl, 150 mmol/L NaCl, 0.1% azide, 1% BSA; pH 7.8) for 1 hour. Plates were subsequently overlayed with primary antibody for 1 hour, washed with PBS, followed by biotinylated anti‐mouse immunoglobulin and streptavidin‐linked alkaline phosphatase as described 11,12 . Working dilutions for MoAbs were 1:10 (MC813‐70), 1:5 (MC631), and neat (B2, RM1).…”

Parvovirus-B19 and hematologic disorders

“…One of these patients progressed to acute lymphoblastic leukemia (ALL), while the other showed total resolution of the blastic morphology and phenotype in the short followup period [72]. A report pointed out the expression of PV-B19 receptor on leukemic cells with a weak association [93]. Temporary effects of the virus on the hematopoietic system may lead to a limited capacity of clonal proliferation, as in our patient with a resolution of ALL.…”

Shiga toxin and its use in targeted cancer therapy and imaging

“…For other cancer types, the patient sample sizes have in general been too small to test for statistical significance. However, as shown in Table 2, a clear tendency towards enhanced Gb3 expression in tumour tissues compared with the corresponding normal tissue has been observed in cancers of the ovary (Farkas‐Himsley et al ., 1995; Arab et al ., 1997), breast (LaCasse et al ., 1999; Johansson et al ., 2009) and pancreas (Distler et al ., 2009), as well as in gliomas (Arab et al ., 1999; Johansson et al ., 2006), malignant meningiomas (Salhia et al ., 2002) and acute non‐lymphocytic leukaemia (Cooling et al ., 2003).…”